The physicochemical properties of the oil from the fruit of Blighia sapida and the toxicological effect of the oil-based diet on some biochemical parameters of selected rat tissues and serum were studied. The smoke, flash, and fire points as well as peroxide, iodine, and acid values of the fruit oil were significantly lower (P < .05), whereas the specific gravity, relative density, saponification, and ester values compared well with soybean oil. The fruit oil yield was 20.02%. The oil consisted of 22.22% saturated, 56.43% monounsaturated, and 21.35% polyunsaturated fatty acids. It is richer than soybean oil in behenic, palmitoleic, oleic, gadoleic, erucic, and 9,12-eicosanoic acids by 15.70%, 0.89%, 7.22%, 12.05%, 8.27%, and 21.35%, respectively. The liver- and kidney-body weight ratios as well as the serum concentrations of cholesterol and high-density lipoprotein cholesterol of the rats maintained on diet formulated with the oil from the fruit of B. sapida increased significantly (P < .05), but the triglyceride and atherogenic index decreased (P < .05). The low-density lipoprotein cholesterol concentration and the heart-body weight ratio of the rats fed with the fruit oil diet compared well (P > .05) with those on soybean oil-based diet. Animals fed with the fruit oil-based diet had their activities of liver glutamate oxaloacetate transaminase and glutamate pyruvate transaminase as well as alkaline phosphatase activities of the liver and kidney decreased with corresponding increase in the serum enzymes. These results suggest that oil from B. sapida fruit could be edible and may be explored as raw materials in the paint, margarine, and soap industries. The oil is also unlikely to predispose the animals to cardiovascular risk, but may labilize the plasma membrane of the hepatocytes and nephrons. It may also have a negative effect on the metabolism and regulation of amino acid in the animals. Therefore, the oil from B. sapida fruit may not be completely safe for consumption.